Sodium Carbonate → 4-(2,5-Difluorobenzyl)-6-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]-1,2,3,4-tetrahydro-[1,8]naphthyridine

HRID 1819123노트

반응식

HRID 1819123 반응식
C([O-])([O-])=O.[Na+].[Na+].Br[C:8]1[CH:9]=[C:10]2[C:15](=[N:16][CH:17]=1)[NH:14][CH2:13][CH2:12][CH:11]2[CH2:18][C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=1[F:26].[CH3:27][N:28]1[CH2:33][CH2:32][N:31]([C:34]2[CH:39]=[CH:38][C:37](B3OC(C)(C)C(C)(C)O3)=[CH:36][N:35]=2)[CH2:30][CH2:29]1>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:26][C:20]1[CH:21]=[CH:22][C:23]([F:25])=[CH:24][C:19]=1[CH2:18][CH:11]1[C:10]2[C:15](=[N:16][CH:17]=[C:8]([C:37]3[CH:36]=[N:35][C:34]([N:31]4[CH2:30][CH2:29][N:28]([CH3:27])[CH2:33][CH2:32]4)=[CH:39][CH:38]=3)[CH:9]=2)[NH:14][CH2:13][CH2:12]1

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 27696181-Methyl-4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazineHCID 578858006-Bromo-4-(2,5-difluorobenzyl)-1,2,3,4-tetrahydro-[1,8]naphthyridine

생성물 1

HCID 469067154-(2,5-Difluorobenzyl)-6-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]-1,2,3,4-tetrahydro-[1,8]naphthyridine수율 26%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 21863594Toluene ethanol용매

실험 절차

Na2CO3 (2N, 53 μL) (4.0 eq) was added to a mixture of 6-bromo-4-(2,5-difluorobenzyl)-1,2,3,4-tetrahydro-[1,8]naphthyridine (9.0 mg) (1 eq), 1-methyl-4-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridin-2-yl]piperazine (11.3 mg) (1.4 eq), and Pd(PPh3)4 (3.0 mg, 0.1 eq) in toluene/ethanol (4:1, v/v, 2 mL). The reaction was heated at 90° C. for six (6) hours. The reaction mixture was then concentrated under reduced pressure and the residue was taken up in CH2Cl2 (15 mL) and washed with water (15 mL). The organic phase was dried over Na2SO4, filtered, concentrated under reduced pressure, and purified by silica gel chromatography using a gradient of 0-20% methanol/CH2Cl2 as the eluting solvent to give the title compound as a yellow foam (26% yield). LCMS: m/z=436 (M+H+), 1H-NMR (CDCl3, 400 MHz) δ 1.7-2.0 (m, 2H), 2.37 (s, 3H), 2.55-2.60 (m, 4H), 2.81 (dd, J=9.1 and 13.3 Hz, 1H), 2.98 (dd, J=6.4 and 13.3H, 1H), 3.08-3.18 (m, 1H), 3.40-3.50 (m, 1H), 3.53-3.70 (m, 5H), 5.18 (bs, 1H), 6.68 (d, J=8.8 Hz, 1H), 6.81-6.87 (m, 1H), 6.89-6.96 (m, 1H), 6.98-7.06 (m, 1H), 7.16 (d, J=1 Hz, 1H), 7.50 (dd, J=2.5 and 8.8 Hz, 1H), 8.05 (d, J=1 Hz, 1H), 8.24 (d, J=2.5 Hz, 1H).

후처리

  1. concentrationThe reaction mixture was then concentrated under reduced pressure
  2. washwashed with water (15 mL)
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. custompurified by silica gel chromatography

출처 및 근거

ORD 기록
ord-53b934f55bc84282bb08ecee29790884
출처 데이터셋
uspto-grants-2009_10
특허 번호
US07601716B2

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